# Temporal Trends in the Management and Mortality Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales: A Cohort Study

## TL;DR

This study tracks changes in KPC-CPE infections and deaths over ten years, showing how treatment and outcomes evolved, especially during the pandemic.

## Contribution

The study provides a decade-long analysis of KPC-CPE management and mortality trends, including treatment shifts and pandemic impacts.

## Key findings

- Infection rates peaked in 2016 and 2023, with a decline during the pandemic.
- Mortality was 28%, with bloodstream infections and ICU admission linked to higher death rates.
- Monotherapy with drugs like ceftazidime-avibactam became more common and was associated with better survival.

## Abstract

Introduction

Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC-CPE) are a significant cause of healthcare-associated infections, characterized by high-level resistance to beta-lactam antibiotics and limited therapeutic options. This study aimed to analyze the epidemiological trends, clinical management, and mortality associated with KPC-CPE infections over a decade, highlighting variations in incidence and treatment patterns during and after the COVID-19 pandemic.

Methods

A retrospective, single-center cohort study was conducted at a tertiary Portuguese hospital, analyzing data from August 2015 to June 2024. Patients with microbiologically confirmed KPC-CPE infections were included in this study. Epidemiological, clinical, and therapeutic data were extracted and analyzed using descriptive statistics and logistic regression to identify risk factors for mortality.

Results

Among 6,259 patients with KPC-CPE isolates, 483 (7.7%) developed infections. Infection rates peaked in 2016 and 2023, with a decline during the COVID-19 pandemic. The 30-day mortality rate was 28%, with bloodstream infections (BSIs) (odds ratio {OR}=1.64, p=0.028) and admission to the intensive care unit (ICU) significantly associated with increased mortality. Urinary tract infections (UTIs) were significantly more frequent in survivors (p=0.001). A shift from combination therapy to monotherapy, particularly with ceftazidime-avibactam (CZA), was observed, aligning with international guidelines. Patients who did not receive adequate antibiotic treatment had significantly higher mortality (OR=6.36, p<0.001). Monotherapy with aminoglycosides, ceftazidime-avibactam, tigecycline, co-trimoxazole (SXT), or fluoroquinolones was more common in survivors. Conversely, combination therapies involving high-dose meropenem (HD-MEM) or aminoglycosides were more common among non-survivors. Mortality was exceptionally high in 2019 and 2020, with no single explanatory factor identified.

Conclusion

Our study findings highlight the importance of rigorous infection control measures, the optimization of antimicrobial therapy, and the continuous surveillance of antimicrobial resistance. The growing reliance on monotherapy underscores the necessity of antimicrobial stewardship programs to prevent the development of resistance. Additional multicenter studies are needed to optimize therapeutic strategies and improve patient outcomes.